{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:43:46Z","timestamp":1787697826318,"version":"build-2784847793"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["F32 AA026480"],"award-info":[{"award-number":["F32 AA026480"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R37 AA018282"],"award-info":[{"award-number":["R37 AA018282"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol: Clinical and Experimental Research"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Excess reactive oxygen species generated by NADPH oxidase 2 (Nox2) in response to ethanol exposure mediate aspects of skeletal toxicity including increased osteoclast differentiation and activity. Because perturbation of chondrocyte differentiation in the growth plate by ethanol could be prevented by dietary antioxidants, we hypothesized that Nox2 in the growth plate was involved in ethanol\u2010associated reductions in longitudinal bone growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nox2 conditional knockout mice were generated, where the essential catalytic subunit of Nox2, cytochrome B\u2010245 beta chain (Cybb), is deleted in chondrocytes using a Cre\u2010Lox model with Cre expressed from the collagen 2a1 promoter (Col2a1\u2010Cre). Wild\u2010type and Cre\u2010Lox mice were fed an ethanol Lieber\u2010DeCarli\u2010based diet or pair\u2010fed a control diet for 8\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ethanol treatment significantly reduced the number of proliferating chondrocytes in the growth plate, enhanced bone marrow adiposity, shortened femurs, reduced body length, reduced cortical bone volume, and decreased mRNA levels of a number of osteoblast and chondrocyte genes. Conditional knockout of Nox2 enzymatic activity in chondrocytes did not consistently prevent any ethanol effects. Rather, knockout mice had fewer proliferating chondrocytes than wild\u2010type mice in both the ethanol\u2010 and control\u2010fed animals. Additional analysis of tibia samples from Nox4 knockout mice showed that loss of Nox4 activity also reduced the number of proliferating chondrocytes and altered chondrocyte size in the growth plate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although Nox enzymatic activity regulates growth plate development, ethanol\u2010associated disruption of the growth plate morphology is independent of ethanol\u2010mediated increases in Nox2 activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15203","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T01:40:46Z","timestamp":1696297246000},"page":"2233-2247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Deletion of <scp>NADPH<\/scp> oxidase 2 in chondrocytes exacerbates ethanol\u2010mediated growth plate disruption in mice without major effects on bone architecture or gene expression"],"prefix":"10.1111","volume":"47","author":[{"given":"K.","family":"Pedersen","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Science Center  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-6522","authenticated-orcid":false,"given":"J.","family":"Watt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Science Center  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Maimone","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Science Center  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Science Center  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Denys","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Science Center  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Schroder","sequence":"additional","affiliation":[{"name":"Institute of Physiology I Goethe\u2010University  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. J.","family":"Suva","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010R.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-3771","authenticated-orcid":false,"given":"M. J. 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